Publications

Autism spectrum disorder (ASD) exhibits an ∼4:1 male-to-female sex bias and is characterized by early-onset impairment of social/communication skills, restricted interests, and stereotyped behaviors. Disruption of the Xp22.11 locus has been associated with ASD in males. This locus includes the three-exon PTCHD1, an adjacent multi-isoform long noncoding RNA (lncRNA) named PTCHD1-AS (spanning ∼1 Mb), and a poorly characterized single-exon RNA helicase named DDX53 that is intronic to PTCHD1-AS....

Autism spectrum disorder (ASD) displays a notable male bias in prevalence. Research into rare (<0.1) genetic variants on the X chromosome has implicated over 20 genes in ASD pathogenesis, such as MECP2, DDX3X, and DMD. The "female protective effect" in ASD suggests that females may require a higher genetic burden to manifest symptoms similar to those in males, yet the mechanisms remain unclear. Despite technological advances in genomics, the complexity of the biological nature of sex chromosomes...

The incorporation of sequencing technologies in frontline and public health healthcare settings was vital in developing virus surveillance programs during the Coronavirus Disease 2019 (COVID-19) pandemic caused by transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, increased data acquisition poses challenges for both rapid and accurate analyses. To overcome these hurdles, we developed the SARS-CoV-2 Illumina GeNome Assembly Line (SIGNAL) for quick bulk...

BACKGROUND: Gliomas are a major cause of cancer-related death among children, adolescents, and young adults (age 0-40 years). Primary mismatch repair deficiency (MMRD) is a pan-cancer mechanism with unique biology and therapeutic opportunities. We aimed to determine the extent and impact of primary MMRD in gliomas among children, adolescents, and young adults.

The eukaryotic CCR4-NOT deadenylase complex is a highly conserved regulator of mRNA metabolism that influences the expression of the complete transcriptome, representing a prime target for a generalist bacterial pathogen. We show that a translocated bacterial effector protein, PieF (Lpg1972) of Legionella pneumophila, directly interacts with the CNOT7/8 nuclease module of CCR4-NOT, with a dissociation constant in the low nanomolar range. PieF is a robust in vitro inhibitor of the DEDD-type...

Site-selective O-arylations of glycoside-derived diols have been achieved by couplings with bromoarenes upon irradiation with blue LEDs in the presence of an iridium photocatalyst and a nickel complex. The use of hexamethylenetetramine (hexamine) in place of quinuclidine, along with the application of a methoxy-substituted 2,2'-bipyridine ligand, provided improvements in yield for this relatively challenging substrate class. Selective arylation took place at the less sterically hindered OH...

Antibody-based research applications are critical for biological discovery. Yet there are no industry standards for comparing the performance of antibodies in various applications. We describe a knockout cell line-based antibody characterization platform, developed and approved jointly by industry and academic researchers, that enables the systematic comparison of antibody performance in western blot, immunoprecipitation and immunofluorescence. The scalable protocols, which require minimal...

Alternative splicing is essential for plants, enabling a single gene to produce multiple transcript variants to boost functional diversity and fine-tune responses to environmental and developmental cues. At-RS31, a plant-specific splicing factor in the Serine/Arginine (SR)-rich protein family, responds to light and the Target of Rapamycin (TOR) signaling pathway, yet its downstream targets and regulatory impact remain unknown.To identify At-RS31 targets, we applied individual-nucleotide...

Here, we describe an innovative and efficient method for screening peptide activators of G-protein-coupled receptors (GPCRs) utilizing a protein-protein interaction (PPI) approach. We designed a library of 92,918 peptides fused with transmembrane domains of glycosylphosphatidylinositol-anchored proteins (GPI-APs). We employed a pooled lentiviral system to promote the expression of these proteins at the cellular membrane and evaluate their ability to activate GPCRs. We then used...

INTRODUCTION: The agriculture genomics community has numerous data submission standards available, but the standards for describing and storing single-cell (SC, e.g., scRNA- seq) data are comparatively underdeveloped.

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Various birth characteristics may influence healthy childhood development, including the risk of developing childhood brain tumors (CBTs). In this study, we aimed to investigate the association between delivery methods, obstetric history, and birth anthropometrics with the risk of CBTs. This study used data from the Childhood Brain Tumour Epidemiology Study of Ontario (CBREO) which included children 0-15 years of age and newly diagnosed with CBTs from 1997 to 2003. Multivariable logistic...

CONCLUSION: The Genetics Adviser is a comprehensive, interactive, patient-centered application found to have high acceptability and usability for pre- and post-test genomic testing, counseling, and return of results adaptable for multiple testing platforms, populations, and settings.

Copy-number variants (CNVs) that increase the risk for neurodevelopmental disorders also affect cognitive ability. However, such CNVs remain challenging to study due to their scarcity, limiting our understanding of gene-dosage-sensitive biological processes linked to cognitive ability. We performed a genome-wide association study (GWAS) in 258,292 individuals, which identified-for the first time-a duplication at 2q12.3 associated with higher cognitive performance. We developed a...

CONCLUSION: GS provided a modest increase in utility after first-tier cancer gene panels, at the cost of a high frequency of uncertain results. Furthermore, most positives were low/moderate cancer risk results that did not have corresponding evidence-based, management guidelines.

The aim of this study is to investigate the prognostic role of body mass index (BMI) on survival from head and neck cancer (HNC). We performed a pooled analysis of studies included in the International Head and Neck Cancer Epidemiology consortium. We used Cox proportional hazards models to estimate the adjusted hazard ratios (HR) for overall survival and HNC-specific survival, and we stratified the results according to cancer site. The study included 10,177 patients from 10 studies worldwide....

RNA-modifying enzymes have recently garnered considerable attention due to their relevance in cancer biology, identifying them as potential targets for novel therapeutic intervention. THUMPD3 was recently identified as an RNA methyltransferase catalysing N2-methylguanosine (m2G) within certain tRNAs. In this study, we unveil a novel role for THUMPD3 in lung cancer cells. Depletion of the enzyme from lung cancer cells significantly impairs their fitness, negatively impacting key cellular...

Immunosuppression by adenosine is an important cancer immune checkpoint. Extracellular adenosine signals through specific receptors and can be transported across the cell membrane through nucleoside transporters. While adenosine receptors are well-known to regulate tumor immunity, the impact of adenosine transporters remains unexplored. In this study, we investigated the effect on tumor immunity of equilibrative nucleoside transporter-1 (ENT1), the major regulator of extracellular adenosine...

CONCLUSIONS: Our findings highlight various patient factors, including vaccination, which contribute to robust, durable SARS-CoV-2 antibody responses. Overall, the findings presented here may inform future vaccine development and rollout plans.

CONCLUSIONS: This first-in-children phase 1 clinical trial demonstrates the safety and feasibility of NAc-DBS in children with severe, refractory SIB at high risk of physical injury and death and supports further investigations.